The Molecular Imaging Program (MIP) consists of 19 members from 7 different departments. Since the last funding cycle the research base of the Program increased 46% from $5,740,595 total annual direct research support, of which $6,393,909 Is from the NCI. Over this last grant period, there were 188 publications of the Molecular Imaging Program, of which 28,7% were intra-programmatic and 36,7% were inter-programmatic. The program has made significant advances in developing novel technologies that facilitate diagnosis and treatment of cancer, and also has provided methodologies and reagents wherein the efficacy of various therapeutics can be monitored in real-time in pre-clinical and clinical settings. These advances include the development of novel molecular Imaging reporter molecules which have Improved our understanding of cancer etiology, biology, pathophysiology and therapy. We will continue to develop cutting edge approaches for imaging the presence of pre-malignant (dysplastic) tissue and oncogenic signaling molecules in vivo. We have developed an Integrated optical molecular Imaging strategy that uses fluorescence peptides as probes to target the presence of pre-malignant (dysplastic) tissue in vivo. The recruitment of Thomas Wang MD, PhD from Stanford University provides the MIP with new capabilities, especially the development of novel optical Imaging probes and instrumentation that can be used as a diagnostic cancer screen for early detection in variousorgans. Drs Ross, Rehemtulla and Luker will continue to develop and validate molecular imaging reporters (i.e. CXCR, c-Met and Akt), Non-invasive imaging in cells and animals will be used to evaluate these novel reporter constructs for detection of key oncogenic signaling pathways. These tools and concepts should significantly aid in our preclinical drug development process and provide insights into more efficacious combination therapy strategies for tumors. Drs Ross, Meyer and Chenevert will continue to develop novel MR-imaging based surrogates for quantification of early therapeutic efficacy in cancer patients. Recent breakthroughs in this area include the concept that analysis of changes within individual voxels (parametric response mapping, PRM) over time, provide a much more robust and predictive quantitative measure of treatment response than current approaches. Application of the PRM concept to clinical trials in brain, breast, head and neck as well as in prostate cancer metastatic to bone, have yielded results that demonstrate the early predictive power of MR-imaging especially when combined with PRM analysis.